Long-lasting Symptoms After an Acute COVID-19 Infection and Factors Associated With Their Resolution
Authors: Olivier Robineau, Marie Zins, Mathilde Touvier, Emmanuel Wiernik, Cedric Lemogne, Xavier de Lamballerie, Hélène Blanché, Jean-François Deleuze, Paola Mariela Saba Villarroel, Céline Dorival, Jerome Nicol, Roselyn Gomes-Rima, Emmanuelle Correia, Mireille Coeuret-Pellicer, Nathalie Druesne-Pecollo, Younes Esseddik, Céline Ribet, Marcel Goldberg, Gianluca Severi, Fabrice Carrat, Fabrice Carrat, Marie Zins, Gianluca Severi, Mathilde Touvier, Hélène Blanché, Jean-François Deleuze, Xavier De Lambalerie, Clovis Lusivika-Nzinga, Gregory Pannetier, Nathanael Lapidus, Isabelle Goderel, Céline Dorival, Jerome Nicol, Olviier Robineau, Sofiane Kab, Adeline Renuy, Stéphane Le-Got, Céline Ribet, Miereille Pellicer, Emmanuel Wiernik, Marcel Goldberg, Fanny Artaud, Pascale Gerbouin-Rérolle, Mélodie nguix, Camille Laplanche, Roselyn Gomes-Rima, Lyan Hoang, Emmanuelle Correia, Alpha Amadou Barry, Nadège Senina, Julien Allegre, Fabien Szabo de Edelenyi, Nathalie Druesne-Pecollo, Yunes Esseddik, Serge Hercberg, Mélanie Deschasaux, Jean-Marc Sébaoun, Jean-Christophe Baudouin, Laetitia Gressin, Valérie Morel, Ouissam Ouili, Laetitia Ninove, Stéphane Priet, Paola Mariela Saba Villarroel, Toscane Fourié, Souand Mohamed Ali, Abdenour Amroun, Morgan Seston, Nazli Ayhan, Boris Pastorino
Journal: JAMA Network Open (2022)

Importance Persistent symptoms after SARS-CoV-2 infection are an emerging public health problem. The duration of these symptoms remains poorly documented. Objective To describe the temporal dynamics of persistent symptoms after SARS-CoV-2 infection and the factors associated with their resolution. Design, Setting, and Participants This cross-sectional study involved 53 047 participants from 3 French adult population-based cohorts (CONSTANCES [Consultants des Centres d’Examens de Santé], E3N/E4N, and Nutrinet-Santé) who were included in a nationwide survey about SARS-CoV-2 infection. All participants were asked to complete self-administered questionnaires between April 1 and June 30, 2020. Variables included sociodemographic characteristics, comorbid conditions, COVID-19 diagnosis, and acute symptoms. Blood samples were obtained for serologic analysis between May 1 and November 30, 2020, from patients with SARS-CoV-2 infection defined as enzyme-linked immunosorbent assay immunoglobulin G antispike detection confirmed with a neutralization assay. A follow-up internet questionnaire was completed between June 1 and September 30, 2021, with details on persistent symptoms, their duration, and SARS-CoV-2 infection diagnosis by polymerase chain reaction. Main Outcomes and Measures Persistent symptoms were defined as symptoms occurring during the acute infection and lasting 2 or more months. Survival models for interval-censored data were used to estimate symptom duration from the acute episode. Multivariable adjusted hazard ratios (HRs) were estimated for age, sex, and comorbid conditions. Factors associated with the resolution of symptoms were assessed. Results A total of 3972 participants (2531 women [63.7%; 95% CI, 62.2%-65.2%]; mean [SD] age, 50.9 [12.7] years) had been infected with SARS-CoV-2. Of these 3972 participants, 2647 (66.6% [95% CI, 65.1%-68.1%]) reported at least 1 symptom during the acute phase. Of these 2647 participants, 861 (32.5% [95% CI, 30.8%-34.3%]) reported at least 1 persistent symptom lasting 2 or more months after the acute phase. After 1 year of follow-up, the estimated proportion of individuals with complete symptom resolution was 89.9% (95% CI, 88.7%-90.9%) with acute symptoms. Older age (&amp;amp;gt;60 years; HR, 0.78; 95% CI, 0.68-0.90), female sex (HR, 0.64; 95% CI, 0.58-0.70), history of cancer (HR, 0.61; 95% CI, 0.47-0.79), history of tobacco consumption (HR, 0.80; 95% CI, 0.73-0.88), high body mass index (≥30: HR, 0.75; 95% CI, 0.63-0.89), and high number of symptoms during the acute phase (&amp;amp;gt;4; HR, 0.43; 95% CI, 0.39-0.48) were associated with a slower resolution of symptoms. Conclusions and Relevance In this cross-sectional study, persistent symptoms were still present in 10.1% of infected individuals at 1 year after SARS-CoV-2 infection. Given the high level of cumulative incidence of COVID-19, the absolute prevalent number of people with persistent symptoms is a public health concern.